- Usefulness of Deep Learning Analysis for the Diagnosis of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas. [Journal Article]
- CTClin Transl Gastroenterol 2019 May 22; 10(5):1-8
- CONCLUSIONS: AI via deep learning algorithm may be a more accurate and objective method to diagnose malignancies of IPMNs in comparison to human diagnosis and conventional EUS features.
- Is the Real Prevalence of Pancreatic Neuroendocrine Tumors Underestimated? A Retrospective Study on a Large Series of Pancreatic Specimens. [Journal Article]
- NNeuroendocrinology 2019 May 22; :1-6
- CONCLUSIONS: The frequency of incidental histological diagnosis of PanNET is considerably high, suggesting that their real prevalence is probably underestimated. The present study suggests a possible correlation between the incidental occurrence of PanNET and IPMN.
- lncRNA H19 binds VGF and promotes pNEN progression via PI3K/AKT/CREB signaling. [Journal Article]
- EREndocr Relat Cancer 2019 Jul 01; 26(7):643-658
- Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tum…
Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain undefined. Microarray analysis was conducted to identify the differentially expressed lncRNAs in pNENs. H19 expression was analyzed in 39 paired pNEN tissues by qPCR. The biological role of H19 was determined by functional experiments. RNA pulldown, mass spectroscopy and RNA immunoprecipitation were performed to confirm the interaction between H19 and VGF. RNA-seq assays were performed after knockdown H19 or VGF. H19 was significantly upregulated in pNEN tissues with malignant behaviors, and the upregulation predicted poor prognosis in pNENs. In vitro and in vivo data showed that H19 overexpression promoted tumor growth and metastasis, whereas H19 knockdown led to the opposite phenotypes. H19 interacted with VGF, which was significantly upregulated in pNENs, and higher VGF expression was markedly related to poor differentiation and advanced stage. Furthermore, VGF was downregulated when H19 was knocked down, and VGF promoted cell proliferation, migration and invasion. Mechanistic investigations revealed that H19 activated PI3K/AKT/CREB signaling and promoted pNEN progression by interacting with VGF. These findings indicate that H19 is a promising prognostic factor in pNENs with malignant behaviors and functions as an oncogene via the VGF-mediated PI3K/AKT/CREB pathway. In addition, our study implies that VGF may also serve as a candidate prognostic biomarker and therapeutic target in pNENs.
- NCCN Guidelines Updates: Pancreatic Cancer. [Journal Article]
- JNJ Natl Compr Canc Netw 2019 May 01; 17(5.5):603-605
- Outcomes for pancreatic cancer are becoming less discouraging with the refinement of molecular profiling, both germline and somatic, and beneficial effects seen with adjuvant chemotherapy. The NCCN G…
Outcomes for pancreatic cancer are becoming less discouraging with the refinement of molecular profiling, both germline and somatic, and beneficial effects seen with adjuvant chemotherapy. The NCCN Guidelines for Pancreatic Adenocarcinoma reflect these advances, and recommend that clinicians consider germline testing for all patients with pancreatic cancer and consider a molecular analysis for those with metastatic disease. The guidelines further recommend that clinicians consider adjuvant therapy with modified FOLFIRINOX (leucovorin/5-FU/irinotecan/oxaliplatin) for patients who are able to tolerate it.
- ASO Author Reflections: The Accurate Prognostic Evaluation and Optimal Treatment Strategy for Ampulla of Vater Carcinoma. [Journal Article]
- ASAnn Surg Oncol 2019 May 21
- Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. [Journal Article]
- IJInt J Mol Med 2019 May 21
- Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to ca…
Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)‑mediated toxicity in hTERT‑HPNE and AsPC‑1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0‑100 µM) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 µM was used. Non‑linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 µM compared to 42 µM in the AsPC‑1 cells (P<0.01). The CdCl2‑mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC‑1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell‑dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.
- MicroRNA hsa-miR-623 directly suppresses MMP1 and attenuates IL-8-induced metastasis in pancreatic cancer. [Journal Article]
- IJInt J Oncol 2019 May 17
- Matrix metalloproteinase‑1 (MMP1) participates in the metastasis of pancreatic cancer, and its expression can be regulated by endogenous microRNAs (miRs/miRNAs) and exogenous inflammatory factors. Wh…
Matrix metalloproteinase‑1 (MMP1) participates in the metastasis of pancreatic cancer, and its expression can be regulated by endogenous microRNAs (miRs/miRNAs) and exogenous inflammatory factors. Whether miRNAs that potentially modulate MMP1 expression can also attenuate the pro‑metastatic effects of its inducer on pancreatic cancer is yet to be completely elucidated. In the present study, a systematic analysis including in silico and bioinformatics analyses, a luciferase reporter assay and an RNA electrophoretic mobility shift assay (EMSA), were used to investigate the interaction between miRNAs and MMP1 mRNA. In addition, wound‑healing assays, Transwell assays and xenograft nude mouse models were implemented to investigate the antitumor activities exerted by candidate miRNAs. As a result, hsa‑miR‑623 was screened as a candidate miRNA that interacts with the MMP1 transcript, and an inverse correlation between the expression of hsa‑miR‑623 and MMP1 was observed in human pancreatic cancer tissue samples. The EMSA confirmed that hsa‑miR‑623 was able to directly bind to its cognate target within the 3'‑untranslated region of the MMP1 transcript. In addition, transfection of hsa‑miR‑623 mimics into PANC‑1 and BXPC‑3 cell lines markedly inhibited the expression of MMP1 at the mRNA and protein levels, and attenuated IL‑8‑induced MMP1 expression. hsa‑miR‑623 also decreased IL‑8‑induced epithelial‑mesenchymal transition in PANC‑1 and BXPC‑3 cells via the underlying mechanism of inhibition of ERK phosphorylation. Consequently, hsa‑miR‑623 inhibited pancreatic cancer cell migration and invasion in vitro and metastasis in vivo. The results of the present study suggest that hsa‑miR‑623 represents a novel adjuvant therapeutic target to prevent metastasis in pancreatic cancer.
- A prospective comparison of conventional cytology and digital image analysis for the identification of pancreatic malignancy in patients undergoing EUS-FNA. [Journal Article]
- EUEndosc Ultrasound 2019 May 09
- CONCLUSIONS: In this study, we demonstrated that DIA provided comparable diagnostic performance to CC in detecting PC. This objective diagnostic method, DIA, emerged as an important supplementary tool to endoscopic biopsy and cytology for diagnosing patients undergoing EUS-FNA with suspected pancreatic malignancy.
- High diagnostic adequacy and accuracy of the new 20G procore needle for EUS-guided tissue acquisition: Results of a large multicentre retrospective study. [Journal Article]
- EUEndosc Ultrasound 2019 May 09
- CONCLUSIONS: The 20G PC needle showed high diagnostic adequacy and accuracy, regardless the access route.
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- Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer. [Journal Article]
- MCMinerva Chir 2019 May 20
- CONCLUSIONS: It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.